Tumour treating fields therapy for glioblastoma: current advances and future directions

Abstract

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles—to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.

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Fig. 1: Historical timeline of the emergence of TTFields as novel therapy for GBM patients.
Fig. 2: The Optune system.
Fig. 3: Summary of the mechanisms of action of TTFields.

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O.R. and S.p.J.C. conceptualised the review. A.V., O.R. and S.p.J.C. contributed to writing early drafts of the paper. All authors contributed to writing–review and editing the paper.

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Correspondence to Ola Rominiyi or Spencer James Collis.

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O.R. and S.p.J.C. are recipients of an Inovitro™ system (on loan from Novocure) and take part in the annual Inovitro™ Users Meeting hosted by Novocure. The remaining authors declare no competing interests.

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O.R. and S.p.J.C. acknowledge funding support from the Royal College of Surgeons, Neurocare, Yorkshire’s Brain Tumour Charity (formerly BTRS) and The Brain Tumour Charity. O.R., S.p.J.C. and C.B. acknowledge funding support from Sheffield Hospitals Charity. O.R., A.V., Y.A.T. and S.p.J.C. are supported by the NIHR Sheffield Biomedical Research Centre/NIHR Sheffield Clinical Research Facility, and all the authors wish to acknowledge kind funding support to cover the costs of publication provided by the NIHR Sheffield Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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Rominiyi, O., Vanderlinden, A., Clenton, S.J. et al. Tumour treating fields therapy for glioblastoma: current advances and future directions. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-01136-5

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